Pretreatment with Human Lactoferrin Had a Positive Effect on the Dynamics of Mouse Nigrostriatal System Recovery after Acute MPTP Exposure

Abstract

We studied the effect of human lactoferrin (hLf) on degenerative changes in the nigrostriatal system and associated behavioral deficits in the animal model of Parkinson disease. Nigrostriatal dopaminergic injury was induced by single administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 40 mg/kg) to five-month-old C57Bl/6 mice. Behavioral disturbances were assessed in the open field and rotarod tests and by the stride length analysis. Structural deficits were assessed by the counts of tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra and optical density (OD) of TH-immunolabeled fibers in the striatum. Acute MPTP treatment induced long-term behavioral deficit and degenerative changes in the nigrostriatal system. Pretreatment with hLf prevented body weight loss and promoted recovery of motor functions and exploratory behavior. Importantly, OD of TH-positive fibers in the striatum of mice treated with hLf almost returned to normal, and the number of TH-positive cells in the substantia nigra significantly increased on day 28. These results indicate that hLf produces a neuroprotective effect and probably stimulates neuroregeneration under conditions of MPTP toxicity in our model. A relationship between behavioral deficits and nigrostriatal system disturbances at delayed terms after MPTP administration was found.

Keywords

• human lactoferrin
• Parkinson’s disease
• MPTP
• substantia nigra
• striatum
• dopaminergic neurons